Introduction

Neural Development

The term gliogenesis refers to the development of the many different types of glial cells within the developing and adult nervous system (CNS and PNS) including: radial glia, astrocytes, oligodendrocytes, Schwann cells, and microglia. Within the neural tube stem cells generate the 2 major classes of cells that make the majority of the nervous system: neurons and most CNS glia. Both these classes of cells differentiate into many different types generated with highly specialized functions and shapes.

Glia (Greek, glia = "glue") and neurons have the same general embryonic origin, generated from neural tube ventricular layer stem cells and neural crest. The developmental process of glial cell development is described as gliogenesis. Glial cells have important roles in neural development and in the adult nervous system and have come a long way from their original description as "supportive cells".

Myelination is the process of close wrapping around a neural axon by a glial cell. This second process occurs as a late feature of glial and nervous system development in both the central and peripheral nervous system and has mainly been studied in relation to demyelinating diseases, such as multiple sclerosis.

Development of the neural crest and sensory systems (hearing/vision/smell) are only briefly introduced in these notes and are covered in detail in another notes sections. (More? neural crest | sensory).

Some Recent Findings

Strong sonic hedgehog signaling in the mouse ventral spinal cord is not required for oligodendrocyte precursor cell (OPC) generation but is necessary for correct timing of its generation[1] "In the mouse neural tube, sonic hedgehog (Shh) secreted from the floor plate (FP) and the notochord (NC) regulates ventral patterning of the neural tube, and later is essential for the generation of oligodendrocyte precursor cells (OPCs). During early development, the NC is adjacent to the neural tube and induces ventral domains in it, including the FP. In the later stage of development, during gliogenesis in the spinal cord, the pMN domain receives strong Shh signaling input. While this is considered to be essential for the generation of OPCs, the actual role of this strong input in OPC generation remains unclear. Here we studied OPC generation in bromi mutant mice which show abnormal ciliary structure. ...The number of OPCs was also significantly decreased in the E12.5 and E14.5 bromi mutant spinal cord. In contrast, motor neuron (MN) production, detected by HB9 expression, significantly increased. It is likely that the transition from MN production to OPC generation in the pMN domain is impaired in bromi mutant mice. These results suggest that strong Shh input to the pMN domain is not required for OPC generation but is essential for producing a sufficient number of OPCs."

Emx2 and Foxg1 inhibit gliogenesis and promote neuronogenesis[2] " Neural stem cells (NSCs) give rise to all cell types forming the cortex: neurons, astrocytes, and oligodendrocytes. The transition from the former to the latter ones takes place via lineage-restricted progenitors in a highly regulated way."

A common progenitor for retinal astrocytes and oligodendrocytes[3] "Here we use retroviruses to label clones of glial cells in the chick retina. We found that almost every clone had both astrocytes and oligodendrocytes. In addition, we discovered a novel glial cell type, with features intermediate between those of astrocytes and oligodendrocytes, which we have named the diacyte. Diacytes also share a progenitor cell with both astrocytes and oligodendrocytes."

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.

This search now requires a manual link as the original PubMed extension has been disabled.

The displayed list of references do not reflect any editorial selection of material based on content or relevance.

References also appear on this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. {More? References | Discussion Page | Journal Searches)

Radial Glia

Radial glia were historically identified by Wilhelm His in 1880's studies of the human fetal brain using classical Golgi silver impregnation histology and were postulated to have a role in the developing central nervous system. It was not until Paso Rakic's much later studies in the 1970's[6][7] (see review[8]) that this roel was confirmed. These cells have an important role in nervous system development, guiding newly formed neurons from their birth zone (ventricular layer) outward to their final adult position. Radial glia generate initially neurons then astrocytes after neurogenesis has been completed.[9][10]

At about 19 weeks (GA 21 weeks) neuronal migration ends and the radial glial cells that aided the migration now become transformed into astrocytes and astrocytic precursors.[11]

Astroglia

Astrocytes are glial cells named by their "star-like" branching appearance, and are the most abundant cells in the brain. They form a key component of the blood-brain barrier and the transfer of circulating nutrients to neurons.

pericytes - (Rouget cells) cells located at the abluminal surface of microvessels close to endothelial cells, mainly found associated with CNS vessels and involved in vessel formation, remodeling and stabilization.

Microglia

Glial cells that act within the central nervous system in the same role as macrophages in other body tissues and act as an innate immune system. There other role is as the cellular mediators of neuroinflammatory processes[16] and cell death[17]. In the mouse embryo, these cells derive from you sac progenitor cells migrating and then proliferating within the CNS.[18][19]

Schwann cells

These cells are named after Theodor Schwann (1810 - 1882), a German physiologist and histologist, who along with Schleiden were early developers of the "cell theory".
Neural crest cells differentiate to form the glial lineage, which in turn generate Schwann cell precursors. (More? Neural Crest Development).

Schwann cells formation is regulated by at least two signals, neuregulin-1 and endothelin. Neuregulins are a family (NRG1, NRG2, NRG3, and NRG4) of EGF-like signaling molecules that bind ErbB receptor tyrosine kinase receptors. Neuregulin-1 type III is expressed on axon surface and has been shown to also regulate Schwann cell membrane growth, adjusting myelin sheath thickness to match axonal calibre.

Fetal - Third Trimester

Three-dimensional magnetic resonance imaging and image-processing algorithms have been used to quantitate between 29-41 weeks volumes of: total brain, cerebral gray matter, unmyelinated white matter, myelinated, and cerebrospinal fluid (grey matter- mainly neuronal cell bodies; white matter- mainly neural processes and glia). A study of 78 premature and mature newborns showed that total brain tissue volume increased linearly over this period at a rate of 22 ml/week. Total grey matter also showed a linear increase in relative intracranial volume of approximately 1.4% or 15 ml/week. The rapid increase in total grey matter is mainly due to a fourfold increase in cortical grey matter. Quantification of extracerebral and intraventricular CSF was found to change only minimally.[23]

Postnatal Neural

Neural development continues after birth with substantial growth, death and reorganization occuring during the postnatally. (More? Postnatal Development - Neural) The references below give a sample of some recent findings and research methods.

Neural induction: old problem, new findings, yet more questions.[24] "During neural induction, the embryonic neural plate is specified and set aside from other parts of the ectoderm. A popular molecular explanation is the 'default model' of neural induction, which proposes that ectodermal cells give rise to neural plate if they receive no signals at all, while BMP activity directs them to become epidermis. However, neural induction now appears to be more complex than once thought, and can no longer be fully explained by the default model alone. This review summarizes neural induction events in different species and highlights some unanswered questions about this important developmental process."

Diffusion tensor imaging of neurodevelopment in children and young adults.[25] "Diffusion tensor magnetic resonance imaging (DTI) was used to study regional changes in the brain's development from childhood (8-12 years, mean 11.1 +/- 1.3, N = 32) to young adulthood (21-27 years, mean 24.4 +/- 1.8, N = 28). ..... These findings suggest a continuation of the brain's microstructural development through adolescence."

Abnormalities

Multiple Sclerosis

Activation of the subventricular zone in multiple sclerosis: evidence for early glial progenitors.[26]"In multiple sclerosis (MS), oligodendrocyte and myelin destruction lead to demyelination with subsequent axonal loss. Experimental demyelination in rodents has highlighted the activation of the subventricular zone (SVZ) and the involvement of progenitor cells expressing the polysialylated form of neural cell adhesion molecule (PSA-NCAM) in the repair process."

Experimental Autoimmune Encephalomyelitis

(EAE) This is an animal model of autoimmune demyelination, such as in multiple sclerosis (MS).[27]

Nogo-A myelin-associated protein which can inhibit neurite outgrowth and prevent regeneration in the adult central nervous system. Secreted by oligodendrocytes in the central nervous system, but not by Schwann cells in the peripheral nervous system. (More? OMIM - Reticulon 4)

Search PubMed

Historic

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.